The proposed research seeks to determine the relationships between the activity of cell membrane enzymes and the control of cellular proliferation. Inhibitors of cell membrane enzymes will be examined in several cell culture systems by comparing the response of untransformed cells which exhibit well-regulated growth properties with the response of neoplastic cells which grow with little or no restraint. Mutant cell populations resistant to the effects of these inhibitors will be selected and their growth characteristics analyzed. The effects on membrane enzyme activity of agents, such as tumor promoters, serum and hormones, which induce cell division will be examined in purified cell membrane preparations. These membrane preparations will also be tested in systems with mammalian RNA polymerases and chromatin to determine if any specific membrane functions are critical for the regulation of transcription in the induction of cell division.